Investigations into inflammatory processes of human disease
Research type
Research Study
Full title
Investigation into the determination of targets responsible for inflammatory processes using human derived peripheral blood mononuclear cells (PBMCs)
IRAS ID
247652
Contact name
Jeanine Harrigan
Contact email
Sponsor organisation
Benevolent AI
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
Research Summary
The purpose of this study is to identify targets that play a role in human inflammatory responses and determine the impact of chemically modulating these targets on human cell mediated immune responses. This is relevant to develop new drugs for a range of diseases that have an inflammatory component such as multiple sclerosis, systemic lupus erythematosus and psoriasis.
To investigate this, we will be performing in vitro studies using human immune cells to investigate whether we observe an effect on the function of these cells following chemical modulation of certain proteins (identified in our computer based screen).
This study will be performed within our in vitro laboratories and we will source the cells from an HTA approved supplier either in the form of freshly isolated cells, cryopreserved cells or whole blood. Samples will be un-identifiable and any donors will be eligible for use.Summary of Results
Ulcerative Colitis and Crohn’s disease are chronic, relapsing, immunologically mediated disorders that are collectively referred to as inflammatory bowel diseases (IBD). The most widely held hypothesis on the pathogenesis of IBD is that overly aggressive acquired T cell immune responses to a subset of commensal enteric bacteria develop in genetically susceptible hosts, and environmental factors precipitate the onset or reactivation of disease. Various immunohistological studies also indicate that macrophages (immune cells) play a role in the disease. To investigate the role of T cells and macrophages in the disease we run studies using human peripheral blood mononuclear cells isolated from blood.
PBMCs were activated with anti-CD3 antibody for T cell activation or lipopolysaccharide (LPS), the major component of Gram-negative bacteria membrane, for macrophage activation.
A total of 174 compounds were tested:
For T cell assay- PBMCs were activated with anti-CD3 antibody
49 compounds show decrease in immune response based on the detected levels of 7 cytokines (IL1-a, IL17a, IFNg, IL-2, IL-4, IL10 and TNFa)
14 compounds show decrease in at least 1 tested cytokine (IL1-a, IL17a, IFNg, IL-2, IL-4, IL10 or TNFa)For macrophage assay- PBMCs were activated with LPS
68 compounds show decrease in in at least 1 tested cytokine (IL1, IL6, or TNFa)None of the compounds that were positive in these assays progressed further to drug development.
REC name
West of Scotland REC 3
REC reference
18/WS/0083
Date of REC Opinion
11 May 2018
REC opinion
Favourable Opinion